10 Dez 2018
16:00 - 17:00
Biozentrum/Pharmazentrum, Lounge, Level E13, Klingelbergstrasse 61, Basel
Self-organization and symmetry breaking in intestinal organoid development
Vortrag von Prof. Dr. Prisca Liberali, SNSF Professor and Research Group Leader Friedrich Miescher Institute for Biomedical Research (FMI), Basel (CH)
Intestinal organoids are complex three-dimensional structures that mimic cell type composition and tissue organization of the intestine by recapitulating the self-organizing capacity of cell populations derived from a single stem cell. Crucial in this process is a first symmetry-breaking event, in which only a fraction of identical cells in a symmetrical cyst differentiate into Paneth cells, which in turn generates the stem cell niche and leads to asymmetric structures such as crypts and villi. We here combine a quantitative single-cell gene expression and imaging approach to characterize the development of intestinal organoids from a single cell. We show that intestinal organoid development follows a regeneration process driven by transient Yap1 activation. Cell-to-cell variability in Yap1, emerging in symmetrical cysts, initiates a Notch/Dll1 lateral inhibition event driving the symmetry-breaking event and the formation of the first Paneth cell. Our findings reveal how single cells exposed to a uniform growth-promoting environment have the intrinsic ability to generate emergent, self-organized behavior resulting in the formation of complex multicellular asymmetric structures.
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